Efficacy of a Ready-to-Feed Starter Liquid Infant Formula Containing 2-Fucosyllactose and Lacto-N-Neotetraose in Chinese Infants: Protocol for a Double Blind, Randomized Controlled Trial.

backgroundBioactive compounds, such as human milk oligosaccharides (HMOs), impact the development of the intestinal microbiome and immune maturation in early life. They have been shown to result in positive benefits, including improved gut health, reduced frequency of infections, and age-appropriate growth when added to infant formula. However, data supporting the added value of including these HMOs in early-stage infant formula is currently lacking among Chinese infants.

objectiveIn this double-blind randomized controlled trial including a nonrandomized reference breastfed group, we will test the efficacy of ready-to-feed infant formula containing 2 HMOs (2-fucosyllactose and lacto-N-neotetraose) on Bifidobacteria abundance, gut microbiome, gut and immune health, growth, and quality of life.

methodsHealthy infants will be enrolled between 3 and 14 days after birth at 5 sites in China and randomized to either the experimental group (fed ready-to-feed infant formula containing 2 HMOs) or the control group (fed the same ready-to-feed infant formula without the 2 HMOs), using a dynamic allocation algorithm with double blinding. Infants will receive trial formula until age 6 months and will be followed up until age 12 months. The breastfed group will serve as a reference. The primary end point will be Bifidobacteria abundance in fecal samples at 3 months, measured via quantitative polymerase chain reaction. Secondary end points will include fecal microbiome (including taxonomy, diversity, functionality, and metabolites), fecal markers of immune health, gastrointestinal tolerance, stooling patterns, immune competence (overall state of the immune system), sleep quality, growth, quality of life, medication use, and physician-reported adverse events. A 2-sided test at the 5% significance level will be used for statistical testing.

resultsThe study received ethical approval in March 2024 and will be completed by the end of 2026, which will be followed by a publication in a peer-reviewed journal.

conclusionsThe Starter Liquid Infant Formula Trial (STARLIT) will be one of the first to assess the efficacy of these 2 HMOs among Chinese infants on gut and immune health, in addition to clinically relevant outcomes such as quality of life, growth, and adverse events. This study should help to demonstrate that an increase in the growth of beneficial Bifidobacteria in response to intake of 2-fucosyllactose and lacto-N-neotetraose may have a broader impact on overall gut microbiome composition and infant gut and immune health.

trial registrationClinicalTrials.gov NCT06361719; https://clinicaltrials.gov/study/NCT06361719. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/66489.